This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Integrins, which are adhesion molecules mediating cell-cell, cell-extracellular matrix, and cell-pathogen interactions, can regulate force-resistant adhesion, polarization in response to extracellular cues, and cell migration by integrating the cytoskeleton of cells with points of attachment in extracellular environments. They are of vital importance to humans and many other organisms because they are related to important physiological processes such as tissue morphogenesis, inflammation, wound healing, and the regulation of cell growth and differentiation. An integrin molecule is a heterodimer with noncovalently associated a- and b-subunits. Nineteen different a-subunits and eight different b-subunits have been reported in vertebrates, forming at least twenty-five ab heterodimers. Integrins are involved in bi-directional signaling processes. They are often in an inactive state in which they bind ligands with low affinity and do not signal, and need to be activated in order to function. According to experimental data, researchers suggest that integrins have multiple conformations and the activation of integrins is accomplished by their conformational change from the bent to the extended. A switch-blade model was provided to explain the conformational change of integrins. However, it is difficult to observe the process of integrin conformational change by experiments. Here, we propose to use molecular dynamics simulations to uncover the pathway of integrin conformational change, and therefore, reveal the structural basis underline integrin activation.